Field of the Invention
The present invention relates to a lung cancer biomarker for diagnosing early stage lung cancers or predicting prognosis of lung cancers, which comprises a GM2AP protein. The present invention also relates to a method for diagnosing early stage lung cancers or predicting prognosis of lung cancers in vitro by detection of the biomarker.
Description of the Related Art
Lung cancer is the leading cause of cancer-related deaths worldwide, accounting for 28% of all male cancer deaths and 26% of all female cancer deaths in the United States in 2013.1 Lung cancer can typically be grouped into two main categories:
small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), accounting for 15% and 85% of lung cancers, respectively. NSCLC consists of three major histological subtypes: adenocarcinoma, squamous cell carcinoma and large cell carcinoma.2 Due to lack of effective early detection tools and ineffective treatments for the advanced stages, the 5-year survival rate of lung cancer is only 15%.3,4 Therefore, early detection is crucial and beneficial for lung cancer patients to receive appropriate and potentially curative treatments.
Tantipaiboonwong et al. first used two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) in search of urinary biomarkers of lung cancer and reported six up-regulated protein spots and three down-regulated protein spots in lung cancer urine samples compared to the controls.5 Among these up-regulated protein spots, the expression of GM2AP level in lung cancer patients was 2.5-4.0 folds higher than that in healthy volunteers. This was consistent with the 2-DE and Western blotting results obtained by Potprommanee et al.6 
GM2-activator protein (GM2AP) is a small monomeric protein containing a single site for Asn linked glycosylation.7 It is first synthesized as a precursor which is then glycosylated, modified and cleaved at 32Ser to be in the mature form. Mature GM2AP is a glycoprotein with molecular mass of 17.6 kDa in its deglycosylated form.8 Acting as a cofactor, GM2AP contains at least three functional features including a hydrophobic pocket called the β-cup structure, an oligosaccharide binding site, and an area that interacts with Hex A.9,10 The area that interacts with Hex A contributes to the degradation of GM2 ganglioside to GM3 by lysosomal β-hexminidase A (Hex A).11,12 However, only one-third of the synthesized of GM2AP is secreted.13,10 Cells can recapture the GM2AP via a carbohydrate-independent mechanism by various cells such as epidermal keratinocytes and fibroblast cells.10 A lack of the functional GM2AP is a cause of the abnormal accumulation of GM2 ganglioside in tissues of patients with the AB variant of GM2 gangliosidosis disease (a severe lysosomal storage disorder).14 The inherited deficiency of GM2AP was also related to the changing level of ganglioside and tumor associated gangliosides involving in cancer progression. Tumor-associated gangliosides are a result of initial oncogenic transformation and play a role in the induction of invasion and metastasis.15,16 Tumor cells synthesized and shed gangliosides into their microenvironments, and this leads to elevated levels of tumor-associated gangliosides in the serum.17,18,19 Moreover, gangliosides are known to exhibit regulatory roles in cell growth, adhesion, cell-cell interactions and signal transduction.20 However, no study has been carried out to investigate the levels of GM2AP and its clinical roles in large number of urine, or biological samples besides urine from patients with lung cancer.